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1.  Spending of HIV resources in Asia and Eastern Europe: systematic review reveals the need to shift funding allocations towards priority populations 
Introduction
It is increasingly important to prioritize the most cost-effective HIV interventions. We sought to summarize the evidence on which types of interventions provide the best value for money in regions with concentrated HIV epidemics.
Methods
We conducted a systematic review of peer-reviewed and grey literature reporting measurements of cost-effectiveness or cost-benefit for HIV/AIDS interventions in Asia and Eastern Europe. We also collated HIV/AIDS spending assessment data from case-study countries in the region.
Results
We identified 91 studies for inclusion, 47 of which were from peer-reviewed journals. Generally, in concentrated settings, prevention of mother-to-child transmission programmes and prevention programmes targeting people who inject drugs and sex workers had lower incremental cost-effectiveness ratios than programmes aimed at the general population. The few studies evaluating programmes targeting men who have sex with men indicate moderate cost-effectiveness. Collation of prevention programme spending data from 12 countries in the region (none of which had generalized epidemics) indicated that resources for the general population/non-targeted was greater than 30% for eight countries and greater than 50% for five countries.
Conclusions
There is a misalignment between national spending on HIV/AIDS responses and the most affected populations across the region. In concentrated epidemics, scarce funding should be directed more towards most-at-risk populations. Reaching consensus on general principles of cost-effectiveness of programmes by epidemic settings is difficult due to inconsistent evaluation approaches. Adopting a standard costing, impact evaluation, benefits calculation, analysis and reporting framework would enable cross comparisons and improve HIV resource prioritization and allocation.
doi:10.7448/IAS.17.1.18822
PMCID: PMC3936108  PMID: 24572053
HIV; cost-benefit analyses; programme evaluation; systematic review; concentrated epidemics; Asia; Eastern Europe; cost-effectiveness
2.  HIV Treatment as Prevention: Principles of Good HIV Epidemiology Modelling for Public Health Decision-Making in All Modes of Prevention and Evaluation 
PLoS Medicine  2012;9(7):e1001239.
Public health responses to HIV epidemics have long relied on epidemiological modelling analyses to help prospectively project and retrospectively estimate the impact, cost-effectiveness, affordability, and investment returns of interventions, and to help plan the design of evaluations. But translating model output into policy decisions and implementation on the ground is challenged by the differences in background and expectations of modellers and decision-makers. As part of the PLoS Medicine Collection “Investigating the Impact of Treatment on New HIV Infections”—which focuses on the contribution of modelling to current issues in HIV prevention—we present here principles of “best practice” for the construction, reporting, and interpretation of HIV epidemiological models for public health decision-making on all aspects of HIV. Aimed at both those who conduct modelling research and those who use modelling results, we hope that the principles described here will become a shared resource that facilitates constructive discussions about the policy implications that emerge from HIV epidemiology modelling results, and that promotes joint understanding between modellers and decision-makers about when modelling is useful as a tool in quantifying HIV epidemiological outcomes and improving prevention programming.
doi:10.1371/journal.pmed.1001239
PMCID: PMC3393657  PMID: 22802729
3.  Cohort Profile: The Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) Study 
The Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) Study was established in 2009 to investigate the associations of sex steroids, inflammation, environmental and psychosocial factors with cardio-metabolic disease risk in men. The study population consists of 2569 men from the harmonisation of two studies: all participants of the Florey Adelaide Male Ageing Study (FAMAS) and eligible male participants of the North West Adelaide Health Study (NWAHS). The cohort has so far participated in three stages of the MAILES Study: MAILES1 (FAMAS Wave 1, from 2002–2005, and NWAHS Wave 2, from 2004–2006); MAILES2 (FAMAS Wave 2, from 2007–2010, and NWAHS Wave 3, from 2008–2010); and MAILES3 (a computer-assisted telephone interview (CATI) survey of all participants in the study, conducted in 2010). Data have been collected on a comprehensive range of physical, psychosocial and demographic issues relating to a number of chronic conditions (including cardiovascular disease, diabetes, arthritis and mental health) and health-related risk factors (including obesity, blood pressure, smoking, diet, alcohol intake and inflammatory markers), as well as on current and past health status and medication. Initial approaches or enquiries regarding the study can be made to either the principal investigator (gary.wittert@adelaide.edu.au) or the project coordinator (sean.martin@adelaide.edu.au).
doi:10.1093/ije/dyt064
PMCID: PMC4258764  PMID: 23785097
Men; cohort studies; longitudinal studies; chronic disease; risk factors
4.  Estimating the Cost-Effectiveness of HIV Prevention Programmes in Vietnam, 2006-2010: A Modelling Study 
PLoS ONE  2015;10(7):e0133171.
Introduction
Vietnam has been largely reliant on international support in its HIV response. Over 2006-2010, a total of US$480 million was invested in its HIV programmes, more than 70% of which came from international sources. This study investigates the potential epidemiological impacts of these programmes and their cost-effectiveness.
Methods
We conducted a data synthesis of HIV programming, spending, epidemiological, and clinical outcomes. Counterfactual scenarios were defined based on assumed programme coverage and behaviours had the programmes not been implemented. An epidemiological model, calibrated to reflect the actual epidemiological trends, was used to estimate plausible ranges of programme impacts. The model was then used to estimate the costs per averted infection, death, and disability adjusted life-year (DALY).
Results
Based on observed prevalence reductions amongst most population groups, and plausible counterfactuals, modelling suggested that antiretroviral therapy (ART) and prevention programmes over 2006-2010 have averted an estimated 50,600 [95% uncertainty bound: 36,300–68,900] new infections and 42,600 [36,100–54,100] deaths, resulting in 401,600 [312,200–496,300] fewer DALYs across all population groups. HIV programmes in Vietnam have cost an estimated US$1,972 [1,447–2,747], US$2,344 [1,843–2,765], and US$248 [201–319] for each averted infection, death, and DALY, respectively.
Conclusions
Our evaluation suggests that HIV programmes in Vietnam have most likely had benefits that are cost-effective. ART and direct HIV prevention were the most cost-effective interventions in reducing HIV disease burden.
doi:10.1371/journal.pone.0133171
PMCID: PMC4510535  PMID: 26196290
5.  Effect of Brassica napus cultivar on cellulosic ethanol yield 
Background
Intraspecific variations in biomass composition are likely to influence their suitability for biorefining. This may be particularly important in species such as Brassica napus, which contain many different crop types bred for different purposes. Here, straw derived from 17 B. napus cultivars, of varying crop types, were steam exploded, saccharified and fermented to establish differences in biomass composition relevant to cellulosic ethanol production.
Results
Despite being grown and processed in the same manner, straw from the various cultivars produced different saccharification and fermentation yields after processing. Fermentation inhibitor abundances released by steam explosion also varied between genotypes. Cultivars with glucan-rich straw did not necessarily produce higher saccharification or ethanol yields after processing. Instead, the compositions of non-cellulosic components were more reliable indicators of substrate quality. The abundance of pectins and arabinogalactans had the greatest influence on saccharification efficiency between straw genotypes.
Conclusions
In dicotyledonous species, such as B. napus, variations in the abundance of pectins between crop cultivars are likely to influence processing efficiency for bioethanol production. Knowledge of these genotypic variants provides targets for plant breeding and could aid in the development of improved cellulase cocktails.
doi:10.1186/s13068-015-0278-z
PMCID: PMC4504093  PMID: 26185525
Bioethanol; Biomass saccharification; Crop cultivars; Cultivar variation; Dicot; Dicotyledonous; Oilseed rape; Fermentation; Pretreatment; Rapeseed straw
6.  Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration 
Ophthalmology  2014;121(7):1435-1444.
Purpose
To detect and quantify choroidal neovascularization (CNV) in age-related macular degeneration (AMD) patients using optical coherence tomography (OCT) angiography.
Design
Observational, cross-sectional study.
Participants
Five normal subjects and five neovascular AMD patients were included.
Methods
Five eyes with neovascular AMD and five normal age-matched controls were scanned by a high-speed (100,000 A-scans/sec) 1050 nm wavelength swept-source OCT. The macular angiography scan covered a 3×3 mm area and comprised 200×200×8 A-scans acquired in 3.5 sec. Flow was detected using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Motion artifacts were removed by three dimensional (3D) orthogonal registration and merging of 4 scans. The 3D angiography was segmented into 3 layers: inner retina (to show retinal vasculature), outer retina (to identify CNV), and choroid. En face maximum projection was used to obtain 2D angiograms from the 3 layers. CNV area and flow index were computed from the en face OCT angiogram of the outer retinal layer. Flow (decorrelation) and structural data were combined in composite color angiograms for both en face and cross-sectional views.
Main Outcome Measurements
CNV angiogram, CNV area, and CNV flow index.
Results
En face OCT angiograms of CNVs showed sizes and locations that were confirmed by fluorescein angiography. OCT angiography provided more distinct vascular network patterns that were less obscured by subretinal hemorrhage. The en face angiograms also showed areas of reduced choroidal flow adjacent to the CNV in all cases and significantly reduced retinal flow in one case. Cross-sectional angiograms were used to visualize CNV location relative to the retinal pigment epithelium and Bruch’s layer and classify type I and type II CNV. A feeder vessel could be identified in one case. Higher flow indexes were associated with larger CNV and type II CNV.
Conclusions
OCT angiography provides depth-resolved information and detailed images of CNV in neovascular AMD. Quantitative information regarding CNV flow and area can be obtained. Further studies are needed to assess the role of quantitative OCT angiography in the evaluation and treatment of neovascular AMD.
doi:10.1016/j.ophtha.2014.01.034
PMCID: PMC4082740  PMID: 24679442
8.  Effect of steam explosion on waste copier paper alone and in a mixed lignocellulosic substrate on saccharification and fermentation 
Bioresource Technology  2015;187:136-143.
Highlights
•Steam explosion of copier paper reduces xylose and produces inhibitors.•Steam explosion at SF 3.6 and 3.9 increased initial rates of saccharification.•Steam explosion at moderate severities may reduce processing times.•Co-steam explosion of waste paper and wheat straw reduces inhibitor production.
This study evaluated steam (SE) explosion on the saccharification and simultaneous saccharification and fermentation (SSF) of waste copier paper. SE resulted in a colouration, a reduction in fibre thickness and increased water absorption. Changes in chemical composition were evident at severities greater than 4.24 resulting in a loss of xylose and the production of breakdown products known to inhibit fermentation (particularly formic acid and acetic acid). SE did not improve final yields of glucose or ethanol, and at severities 4.53 and 4.83 reduced yields probably due to the effect of breakdown products and fermentation inhibitors. However, at moderate severities of 3.6 and 3.9 there was an increase in initial rates of hydrolysis which may provide a basis for reducing processing times. Co-steam explosion of waste copier paper and wheat straw attenuated the production of breakdown products, and may also provide a basis for improving SSF of lignocellulose.
doi:10.1016/j.biortech.2015.03.089
PMCID: PMC4504980  PMID: 25846183
Steam explosion; Enzyme saccharification; Fermentation; SSF; Cellulosic biomass
9.  Differences Determined by Optical Coherence Tomography Volumetric Analysis in Non-Culprit Lesion Morphology and Inflammation in ST-Segment Elevation Myocardial Infarction and Stable Angina Pectoris Patients 
Background
While the current methodology for determining fibrous cap (FC) thickness of lipid plaques is based on manual measurements of arbitrary points, which could lead to high variability and decreased accuracy, it ignores the three-dimensional (3-D) morphology of coronary artery disease.
Objective
To compare, utilizing optical coherence tomography (OCT) assessments, volumetric quantification of FC, and macrophage detection using both visual assessment and automated image processing algorithms in non-culprit lesions of STEMI and stable angina pectoris (SAP) patients.
Methods
Lipid plaques were selected from 67 consecutive patients (1 artery/patient). FC was manually delineated by a computer-aided method and automatically classified into three thickness categories: FC < 65 μm (i.e., thin-cap fibroatheroma [TCFA]), 65–150 μm, and >150 μm. Minimum thickness, absolute categorical surface area, and fractional luminal area of FC were analyzed. Automated detection and quantification of macrophage was performed within the segmented FC.
Results
A total of 5,503 cross-sections were analyzed. STEMI patients when compared with SAP patients had more absolute categorical surface area for TCFA (0.43 ± 0.45 mm2 vs. 0.15 ± 0.25 mm2; P = 0.011), thinner minimum FC thickness (31.63 ± 17.09 μm vs. 47.27 ± 26.56 μm, P = 0.012), greater fractional luminal area for TCFA (1.65 ± 1.56% vs. 0.74 ± 1.2%, P = 0.046), and greater macrophage index (0.0217 ± 0.0081% vs. 0.0153 ± 0.0045%, respectively, P< 0.01).
Conclusion
The novel OCT-based 3-D quantification of the FC and macrophage demonstrated thinner FC thickness and larger areas of TCFA coupled with more inflammation in non-culprit sites of STEMI compared with SAP.
doi:10.1002/ccd.25660
PMCID: PMC4484583  PMID: 25178981
optical coherence tomography; fibrous cap; macrophage; ST-segment elevation myocardial infarction; stable angina; thin-cap fibroatheroma; atherosclerosis
10.  Overexpression of the Cytosolic Form of Phosphoenolpyruvate Carboxykinase (GTP) in Skeletal Muscle Repatterns Energy Metabolism in the Mouse*s⃞♦ 
The Journal of biological chemistry  2007;282(45):32844-32855.
Transgenic mice, containing a chimeric gene in which the cDNA for phosphoenolpyruvate carboxykinase (GTP) (PEPCK-C) (EC 4.1.1.32) was linked to the α-skeletal actin gene promoter, express PEPCK-C in skeletal muscle (1–3 units/g). Breeding two founder lines together produced mice with an activity of PEPCK-C of 9 units/g of muscle (PEPCK-Cmus mice). These mice were seven times more active in their cages than controls. On a mouse treadmill, PEPCK-Cmus mice ran up to 6 km at a speed of 20 m/min, whereas controls stopped at 0.2 km. PEPCK-Cmus mice had an enhanced exercise capacity, with a VO2max of 156 ± 8.0 ml/kg/min, a maximal respiratory exchange ratio of 0.91 ± 0.03, and a blood lactate concentration of 3.7 ± 1.0 mm after running for 32 min at a 25° grade; the values for control animals were 112 ± 21 ml/kg/min, 0.99 ± 0.08, and 8.1 ± 5.0 mm respectively. The PEPCK-Cmus mice ate 60% more than controls but had half the body weight and 10% the body fat as determined by magnetic resonance imaging. In addition, the number of mitochondria and the content of triglyceride in the skeletal muscle of PEPCK-Cmus mice were greatly increased as compared with controls. PEPCK-Cmus mice had an extended life span relative to control animals; mice up to an age of 2.5 years ran twice as fast as 6 −12-month-old control animals. We conclude that overexpression of PEPCK-C repatterns energy metabolism and leads to greater longevity.
doi:10.1074/jbc.M706127200
PMCID: PMC4484620  PMID: 17716967
11.  Robust GRAPPA Reconstruction and Its Evaluation With the Perceptual Difference Model 
Purpose
To develop and optimize a new modification of GRAPPA (generalized autocalibrating partially parallel acquisitions) MR reconstruction algorithm named “Robust GRAPPA”.
Materials and Methods
In Robust GRAPPA, k-space data points were weighted before the reconstruction. Small or zero weights were assigned to “outliers” in k-space. We implemented a Slow Robust GRAPPA method, which iteratively reweighted the k-space data. It was compared to an ad hoc Fast Robust GRAPPA method, which eliminated (assigned zero weights to) a fixed percentage of k-space “outliers” following an initial estimation procedure. In comprehensive experiments the new algorithms were evaluated using the perceptual difference model (PDM), whereby image quality was quantitatively compared to the reference image. Independent variables included algorithm type, total reduction factor, outlier ratio, center filling options, and noise across multiple image datasets, providing 10,800 test images for evaluation.
Results
The Fast Robust GRAPPA method gave results very similar to Slow Robust GRAPPA, and showed significant improvements as compared to regular GRAPPA. Fast Robust GRAPPA added little computation time compared with regular GRAPPA.
Conclusion
Robust GRAPPA was proposed and proved useful for improving the reconstructed image quality. PDM was helpful in designing and optimizing the MR reconstruction algorithms.
doi:10.1002/jmri.21352
PMCID: PMC4484794  PMID: 18504764
GRAPPA; parallel imaging; robust fitting; PDM
12.  HIV Programs for Sex Workers: Lessons and Challenges for Developing and Delivering Programs 
PLoS Medicine  2015;12(6):e1001808.
There is evidence that HIV prevention programs for sex workers, especially female sex workers, are cost-effective in several contexts, including many western countries, Thailand, India, the Democratic Republic of Congo, Kenya, and Zimbabwe. The evidence that sex worker HIV prevention programs work must not inspire complacency but rather a renewed effort to expand, intensify, and maximize their impact. The PLOS Collection “Focus on Delivery and Scale: Achieving HIV Impact with Sex Workers” highlights major challenges to scaling-up sex worker HIV prevention programs, noting the following: sex worker HIV prevention programs are insufficiently guided by understanding of epidemic transmission dynamics, situation analyses, and programmatic mapping; sex worker HIV and sexually transmitted infection services receive limited domestic financing in many countries; many sex worker HIV prevention programs are inadequately codified to ensure consistency and quality; and many sex worker HIV prevention programs have not evolved adequately to address informal sex workers, male and transgender sex workers, and mobile- and internet-based sex workers. Based on the wider collection of papers, this article presents three major clusters of recommendations: (i) HIV programs focused on sex workers should be prioritized, developed, and implemented based on robust evidence; (ii) national political will and increased funding are needed to increase coverage of effective sex worker HIV prevention programs in low and middle income countries; and (iii) comprehensive, integrated, and rapidly evolving HIV programs are needed to ensure equitable access to health services for individuals involved in all forms of sex work.
Reflecting on the "Focus on Delivery and Scale: Achieving HIV Impact with Sex Workers" collection, David Wilson outlines action-oriented recommendations to increase the reach, intensity, and impact of HIV prevention interventions targeted towards sex work.
doi:10.1371/journal.pmed.1001808
PMCID: PMC4469316  PMID: 26079267
13.  WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited 
The Journal of Clinical Investigation  2015;125(3):1269-1285.
Cholangiocarcinoma (CC) is typically diagnosed at an advanced stage and is refractory to surgical intervention and chemotherapy. Despite a global increase in the incidence of CC, little progress has been made toward the development of treatments for this cancer. Here we utilized human tissue; CC cell xenografts; a p53-deficient transgenic mouse model; and a non-transgenic, chemically induced rat model of CC that accurately reflects both the inflammatory and regenerative background associated with human CC pathology. Using these systems, we determined that the WNT pathway is highly activated in CCs and that inflammatory macrophages are required to establish this WNT-high state in vivo. Moreover, depletion of macrophages or inhibition of WNT signaling with one of two small molecule WNT inhibitors in mouse and rat CC models markedly reduced CC proliferation and increased apoptosis, resulting in tumor regression. Together, these results demonstrate that enhanced WNT signaling is a characteristic of CC and suggest that targeting WNT signaling pathways has potential as a therapeutic strategy for CC.
doi:10.1172/JCI76452
PMCID: PMC4362247  PMID: 25689248
14.  Removal of Out-of-Plane Fluorescence for Single Cell Visualization and Quantification in Cryo-Imaging 
Annals of biomedical engineering  2009;37(8):1613-1628.
We developed a cryo-imaging system, which alternates between sectioning (10–40 μm) and imaging bright field and fluorescence block-face image volumes with micronscale-resolution. For applications requiring single-cell detection of fluorescently labeled cells anywhere in a mouse, we are developing software for reduction of out-of-plane fluorescence. In mouse experiments, we imaged GFP-labeled cancer and stem cells, and cell-sized fluorescent microspheres. To remove out-of-plane fluorescence, we used a simplified model of light-tissue interaction whereby the next-image was scaled, blurred, and subtracted from the current image. We estimated scaling and blurring parameters by minimizing an objective function on subtracted images. Tissue-specific attenuation parameters [μT: heart (267 ± 47.6 cm−1), liver (218 ± 27.1 cm−1), brain (161 ± 27.4 cm−1)] were found to be within the range of estimates in the literature. “Next-image” processing removed out-of-plane fluorescence equally well across multiple tissues (brain, kidney, liver, etc.), and analysis of 200 microsphere images gave 97 ± 2% reduction of out-of-plane fluorescence. Next-image processing greatly improved axial-resolution, enabled high quality 3D volume renderings, and improved automated enumeration of single cells by up to 24%. The method has been used to identify metastatic cancer sites, determine homing of stem cells to injury sites, and show microsphere distribution correlated with blood flow patterns.
doi:10.1007/s10439-009-9726-x
PMCID: PMC4452119  PMID: 19513848
Image processing; Block face imaging; Fluorescence imaging; In vivo cellular imaging; Stem cell imaging; Metastatic cancer; GFP imaging
15.  APE1 incision activity at abasic sites in tandem repeat sequences 
Journal of molecular biology  2014;426(11):2183-2198.
Repetitive DNA sequences, such as are present in micro- and mini-satellites, telomeres, and trinucleotide repeats (linked to fragile X syndrome, Huntington disease, etc.), account for nearly 30% of the human genome. These domains exhibit enhanced susceptibility to oxidative attack to yield base modifications, strand breaks and abasic sites, have a propensity to adopt non-canonical DNA forms modulated by the position(s) of the lesion(s), and, when not properly processed, can contribute to genome instability that underlies aging and disease development. Knowledge of the repair efficiencies of DNA damage within such repetitive sequences is therefore crucial for understanding the impact of such domains on genomic integrity. In the present study, using strategically designed oligonucleotide substrates, we determined the ability of human apurinic/apyrimidinic endonuclease 1 (APE1) to cleave at AP sites in a collection of tandem DNA repeat landscapes involving telomeric and CAG/CTG repeat sequences. Our studies reveal the differential influence of domain sequence, conformation, and AP site location/relative positioning on the efficiency of APE1 binding and strand incision. Intriguingly, our data demonstrate that APE1 endonuclease efficiency correlates with the thermodynamic stability of the DNA substrate. We discuss how these results have both predictive and mechanistic consequences for understanding the success and failure of repair protein activity associated with such oxidatively sensitive, conformationally plastic/dynamic repetitive DNA domains.
doi:10.1016/j.jmb.2014.03.014
PMCID: PMC4034141  PMID: 24703901
APEX1; AP or abasic site; tandem repeat; telomere; trinucleotide expansion
16.  Long-range evolutionary constraints reveal cis-regulatory interactions on the human X chromosome 
Nature Communications  2015;6:6904.
Enhancers can regulate the transcription of genes over long genomic distances. This is thought to lead to selection against genomic rearrangements within such regions that may disrupt this functional linkage. Here we test this concept experimentally using the human X chromosome. We describe a scoring method to identify evolutionary maintenance of linkage between conserved noncoding elements and neighbouring genes. Chromatin marks associated with enhancer function are strongly correlated with this linkage score. We test >1,000 putative enhancers by transgenesis assays in zebrafish to ascertain the identity of the target gene. The majority of active enhancers drive a transgenic expression in a pattern consistent with the known expression of a linked gene. These results show that evolutionary maintenance of linkage is a reliable predictor of an enhancer's function, and provide new information to discover the genetic basis of diseases caused by the mis-regulation of gene expression.
Enhancers regulate the transcription of genes over long genomic distances. Here, the authors show that enhancer function is correlated with maintenance of linkage between non-coding elements and neighbouring genes in the human X chromosome and that enhancers in zebrafish drive expression in a pattern consistent with the expression of a linked gene.
doi:10.1038/ncomms7904
PMCID: PMC4423230  PMID: 25908307
17.  Volumetric Characterization of Human Coronary Calcification by Frequency Domain Optical Coherence Tomography 
Background
Coronary artery calcification (CAC) presents unique challenges for percutaneous coronary intervention. Calcium appears as a signal-poor region with well-defined borders by FD-OCT, which might enable full quantification of CAC. The objective of this study was to demonstrate the accuracy of intravascular frequency-domain optical coherence tomography (FD-OCT) to determine distribution of CAC.
Methods and Results
Cadaveric coronary arteries were imaged using FD-OCT at 100Dm frame interval. Arteries were subsequently frozen, sectioned and imaged in their entire length at 20Dm intervals using the Case Cryo-Imaging automated system™. Full volumetric co-registration between FD-OCT and cryo-images was performed. Calcium area, distance from lumen and angle were traced on every cross-section and volumetric quantification was performed offline using a dedicated algorithm.
Thirty left anterior descending (LAD) arteries were imaged by both FD-OCT and cryo-imaging. Of these, 13 vessels had a total of 55 plaques with calcification by cryo-imaging and FD-OCT identified 47 (85%) of these plaques. Quantitative analyses of 1285 cryo-images were compared with corresponding co-registered 257 FD-OCT images. Calcium distribution, represented by the calcium-lumen distance (depth) and the mean calcium angle, was similar with excellent correlation between FD-OCT and cryo-imaging respectively (calcium-lumen distance: 0.25±0.09mm vs. 0.26±0.12mm, p=0.742; R=0.90), (mean calcium angle: 35.33±21.86° vs. 39.68±26.61°, p=0.207; R=0.88). Volumetric quantification of CAC was possible by OCT; calcium volume was underestimated in large calcifications in which the abluminal plaque border could not be well visualized (3.11±2.14mm3 vs. 4.58±3.39mm3, p=0.001) in OCT vs. cryo respectively.
Conclusion
Intravascular FD-OCT can accurately characterize CAC distribution. OCT can quantify absolute calcium volume, but may underestimate calcium burden in large plaques with poorly defined abluminal borders.
PMCID: PMC4422196  PMID: 23782524
Optical coherence tomography; Coronary artery calcification; Cryo-imaging; Percutaneous coronary intervention
18.  Is it time to switch to doxycycline from azithromycin for treating genital chlamydial infections in women? Modelling the impact of autoinoculation from the gastrointestinal tract to the genital tract 
BMC Infectious Diseases  2015;15:200.
Background
Single-dose azithromycin is recommended over multi-dose doxycycline as treatment for chlamydial infection. However, even with imperfect adherence, doxycycline is more effective in treating genital and rectal infection. Recently, it has been suggested that autoinoculation from the rectum to the genitals may be a source of persistent chlamydial infection in women. We estimated the impact autoinoculation may have on azithromycin and doxycycline effectiveness.
Methods
We estimate treatment effectiveness using a simple mathematical model, incorporating data on azithromycin and doxycycline efficacy from recent meta-analyses, and data on prevalence of rectal infection in women with genital chlamydial infection.
Results
When the possibility of autoinoculation is taken into account, we calculate that doxycycline effectiveness may be 97% compared to just 82% for azithromycin.
Conclusions
Consideration should be given to re-evaluating azithromycin as the standard treatment for genital chlamydia in women.
doi:10.1186/s12879-015-0939-3
PMCID: PMC4419407  PMID: 25925662
Chlamydia; Azithromycin; Doxycycline; Re-infection
19.  Quality in clinical cytometry 
doi:10.1186/1476-9255-12-S1-O5
PMCID: PMC4416156
20.  Control of Trachoma in Australia: A Model Based Evaluation of Current Interventions 
PLoS Neglected Tropical Diseases  2015;9(4):e0003474.
Background
Australia is the only high-income country in which endemic trachoma persists. In response, the Australian Government has recently invested heavily towards the nationwide control of the disease.
Methodology/Principal Findings
A novel simulation model was developed to reflect the trachoma epidemic in Australian Aboriginal communities. The model, which incorporates demographic, migration, mixing, and biological heterogeneities, was used to evaluate recent intervention measures against counterfactual past scenarios, and also to assess the potential impact of a series of hypothesized future intervention measures relative to the current national strategy and intensity. The model simulations indicate that, under the current intervention strategy and intensity, the likelihood of controlling trachoma to less than 5% prevalence among 5–9 year-old children in hyperendemic communities by 2020 is 31% (19%–43%). By shifting intervention priorities such that large increases in the facial cleanliness of children are observed, this likelihood of controlling trachoma in hyperendemic communities is increased to 64% (53%–76%). The most effective intervention strategy incorporated large-scale antibiotic distribution programs whilst attaining ambitious yet feasible screening, treatment, facial cleanliness and housing construction targets. Accordingly, the estimated likelihood of controlling trachoma in these communities is increased to 86% (76%–95%).
Conclusions/Significance
Maintaining the current intervention strategy and intensity is unlikely to be sufficient to control trachoma across Australia by 2020. However, by shifting the intervention strategy and increasing intensity, the likelihood of controlling trachoma nationwide can be significantly increased.
Author Summary
Australia is the only remaining high-income country reporting endemic levels of trachoma, with infections occurring predominantly within rural and remote Indigenous communities. Although the Australian government has recently invested large sums of money to combat the disease, it remains unclear whether the national goal of controlling trachoma by 2020 will be achieved. Here, we use a novel individual-based simulation model to estimate the impact of numerous potential future invention strategies and intensities. Our model is the most sophisticated trachoma transmission model to date, and the first to specifically represent trachoma in Australian Indigenous communities. Model projections suggest that although the current intervention strategy and intensity are unlikely to achieve the target of national control by 2020, the likelihood of achieving this goal can be significantly increased by shifting the intervention strategy and increasing the intensity of key intervention components such as screening, treatment and facial cleanliness activities. Our findings that the most resource rich country with endemic trachoma may require a more intensive intervention effort to control the disease suggest that challenges may remain in the fight for the global control and eventual elimination and eradication of trachoma.
doi:10.1371/journal.pntd.0003474
PMCID: PMC4393231  PMID: 25860143
21.  Musculoskeletal Symptoms Amongst Clinical Radiologists and the Implications of Reporting Environment Ergonomics—A Multicentre Questionnaire Study 
Journal of Digital Imaging  2013;27(2):255-261.
This multicentre study aimed to assess compliance of the reporting environment with best ergonomic practice and to determine the prevalence of musculoskeletal symptoms related to working as a radiologist. All 148 radiology trainees and consultants in 10 hospitals across the region were invited to complete a musculoskeletal symptoms and reporting ergonomics questionnaire. Best ergonomic reporting practice was defined, following literature review, as being able to alter the following: monitor, desk, chair and armrest height, chair back support, ambient light, and temperature. The frequency that these facilities were available and how often they were used was determined. One hundred and twenty-three out of 148 (83 %) radiologists responded, and 38 % reported radiology-associated occupational injury. Lower back discomfort was the commonest radiology associated musculoskeletal symptom (41 %). Only 13 % of those with occupational injury sought the advice of occupational health. No reporting environments conformed completely to best ergonomic practice. Where certain facilities were available, less than a third of radiologists made personal ergonomic adjustments prior to starting a reporting session. Radiologists who had good self-assessed knowledge of best ergonomic practice had significantly less back discomfort than those with poor self-assessed knowledge (P < 0.005). We demonstrated high prevalence of musculoskeletal symptoms amongst radiologists. Poor compliance of the reporting environment with best ergonomic practice, in combination with our other findings of a low level of ergonomic awareness, low rates of making ergonomic adjustments and seeking appropriate help, may be implicated. We hope this study raises awareness of this issue and helps prevent long-term occupational injury amongst radiologists from poor ergonomic practice.
doi:10.1007/s10278-013-9642-3
PMCID: PMC3948925  PMID: 24113846
Ergonomics; Musculoskeletal pain; Occupational health; Occupational injury; Radiology
23.  Inhibition of JAK/STAT signaling stimulates adult satellite cell function 
Nature medicine  2014;20(10):1174-1181.
Diminished regenerative capacity of skeletal muscle occurs during adulthood. We identified a reduction in the intrinsic capacity of murine adult satellite cells to contribute to regeneration and repopulate the niche. Gene expression analysis identified an increase in expression of JAK/STAT signaling targets between 3 week old and 18 month old mice. Knockdown of Jak2 or Stat3 significantly stimulated symmetric satellite stem cell divisions on cultured myofibers. Knockdown of Jak2 or Stat3 in prospectively isolated satellite cells markedly enhanced their ability to repopulate the satellite cell niche. Pharmacological inhibition of Jak2 and Stat3 similarly stimulated symmetric expansion of satellite cells in vitro and their engraftment in vivo. Intramuscular injection of these drugs resulted in a dramatic enhancement of muscle repair and force generation. Together these results reveal intrinsic properties that functionally distinguish adult satellite cells and suggest a promising therapeutic avenue for the treatment of muscle wasting diseases.
doi:10.1038/nm.3655
PMCID: PMC4191983  PMID: 25194569
Skeletal muscle; satellite cell; stem cells; aging; JAK/STAT signaling
24.  Parenchymal preserving anatomic resections result in less pulmonary function loss in patients with Stage I non-small cell lung cancer 
Background
A suggested benefit of sublobar resection for stage I non-small cell lung cancer (NSCLC) compared to lobectomy is a relative preservation of pulmonary function. Very little objective data exist, however, supporting this supposition. We sought to evaluate the relative impact of both anatomic segmental and lobar resection on pulmonary function in patients with resected clinical stage I NSCLC.
Methods
The records of 159 disease-free patients who underwent anatomic segmentectomy (n = 89) and lobectomy (n = 70) for the treatment of stage I NSCLC with pre- and postoperative pulmonary function tests performed between 6 to 36 months after resection were retrospectively reviewed. Changes in forced expiratory volume in one second (FEV1) and diffusion capacity of carbon monoxide (DLCO) were analyzed based upon the number of anatomic pulmonary segments removed: 1–2 segments (n = 77) or 3–5 segments (n = 82).
Results
Preoperative pulmonary function was worse in the lesser resection cohort (1–2 segments) compared to the greater resection group (3–5 segments) (FEV1(%predicted): 79% vs. 85%, p = 0.038; DLCO(%predicted): 63% vs. 73%, p = 0.010). A greater decline in FEV1 was noted in patients undergoing resection of 3–5 segments (FEV1 (observed): 0.1 L vs. 0.3 L, p = 0.003; and FEV1 (% predicted): 4.3% vs. 8.2%, p = 0.055). Changes in DLCO followed this same trend (DLCO(observed): 1.3 vs. 2.4 mL/min/mmHg, p = 0.015; and DLCO(% predicted): 3.6% vs. 5.9%, p = 0.280).
Conclusions
Parenchymal-sparing resections resulted in better preservation of pulmonary function at a median of one year, suggesting a long-term functional benefit with small anatomic segmental resections (1–2 segments). Prospective studies to evaluate measurable functional changes, as well as quality of life, between segmentectomy and lobectomy with a larger patient cohort appear justified.
doi:10.1186/s13019-015-0253-6
PMCID: PMC4382835  PMID: 25888465
Pulmonary function; Lung segmentectomy or wedge resection; Lobectomy (lung); Lung cancer; Outcomes
25.  Gene Expressing Profiling of Iris Melanomas 
Ophthalmology  2013;120(1):213-213.e3.
doi:10.1016/j.ophtha.2012.08.016
PMCID: PMC4354954  PMID: 23283188

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