Screening for low bone mineral density in patients with respiratory disease

Patients with respiratory disease have decreased mean bone mineral density (BMD) and thereby increased risk of fractures compared to people without respiratory disease. A clinical screening tool was developed to identify patients unlikely to have low BMD who do not require bone densitometry, and estimated number needed to screen (NNS) and number needed to treat to prevent one hip fracture in this patient group. The screening tool was found to have a high negative predictive value, and therefore may assist clinicians to identify those who would benefit most from densitometry. Using this screening tool together with NNS may enable the development of a cost-effective screening programme for low BMD in respiratory patients.Thesis (M.Med.Sc.) -- University of Adelaide, Dept. of Medicine, 2003

Knee Pain Predicts Subsequent Shoulder Pain and the Association Is Mediated by Leg Weakness: Longitudinal Observational Data from the Osteoarthritis Initiative

Objective: To assess whether the ‘spread’ of joint pain is related to pain-associated muscle loss in one joint leading to increased loading and subsequent pain in other joints. Methods: Associations between persistent knee pain (pain in one or two knees over years 0-3 versus no persistent pain) and incident shoulder pain at year 4 were examined in participants from the longitudinal NIH Osteoarthritis Initiative (OAI). Associations were assessed using log multinomial modelling, adjusted for age, sex, BMI, depression score, other lower limb pain and baseline leg weakness (difficulty standing from a sitting position). Results: In older adults with clinically significant knee OA or at risk of knee OA (n=3486), the number of painful joints increased yearly, from 2.1 joints (95% CI 2.0, 2.2) at baseline increasing by 5.2% (95% CI 2.2%, 8.3%) at year 4. Shoulders were the next most commonly affected joint after knees (28.5%). Persistent pain in 1 or 2 knees increased risk of bilateral shoulder pain at year 4 (1 knee RR 1.59 (95% CI 0.97, 2.61); 2 knees RR 2.02 (1.17, 3.49)) after adjustment for confounders. Further adjustment for leg weakness attenuated effect sizes (1 knee RR 1.13 (95% CI 0.60, 2.11); 2 knees RR 1.44 (0.75, 2.77)), indicating mediation by functional leg weakness. Conclusions: Spread of joint pain is not random. Persistently painful knees predict new bilateral shoulder pain, which is likely mediated by leg weakness; suggesting that biomechanical factors influence the spread of pain

The effect of FTO variation on increased osteoarthritis risk is mediated through body mass index : a mendelian randomisation study

Objective: Variation in the fat mass and obesity-associated (FTO) gene influences susceptibility to obesity. A variant in the FTO gene has been implicated in genetic risk to osteoarthritis (OA). We examined the role of the FTO polymorphism rs8044769 in risk of knee and hip OA in cases and controls incorporating body mass index (BMI) information. Methods: 5409 knee OA patients, 4355 hip OA patients and up to 5362 healthy controls from 7 independent cohorts from the UK and Australia were genotyped for rs8044769. The association of the FTO variant with OA was investigated in case/control analyses with and without BMI adjustment and in analyses matched for BMI category. A mendelian randomisation approach was employed using the FTO variant as the instrumental variable to evaluate the role of overweight on OA. Results: In the meta-analysis of all overweight (BMI≥25) samples versus normal-weight controls irrespective of OA status the association of rs8044769 with overweight is highly significant (OR[CIs] for allele G=1.14 [01.08 to 1.19], p=7.5×10−7). A significant association with knee OA is present in the analysis without BMI adjustment (OR[CIs]=1.08[1.02 to 1.14], p=0.009) but the signal fully attenuates after BMI adjustment (OR[CIs]=0.99[0.93 to 1.05], p=0.666). We observe no evidence for association in the BMI-matched meta-analyses. Using mendelian randomisation approaches we confirm the causal role of overweight on OA. Conclusions: Our data highlight the contribution of genetic risk to overweight in defining risk to OA but the association is exclusively mediated by the effect on BMI. This is consistent with what is known of the biology of the FTO gene and supports the causative role of high BMI in OA

Predictors of total hip replacement in community based older adults : a cohort study

This work was supported by the National Health and Medical Research Council of Australia (NHMRC Grant ID – 302204); Tasmanian Community Fund (Grant ID – D0015018); Masonic Centenary Medical Research Foundation; Royal Hobart Hospital Research Foundation; Arthritis Foundation of Australia (Grant ID – MRI06161); and University of Tasmania institutional research grants scheme (D0015019). The study sponsor had no role in the design of the study; the collection, analysis, and interpretation of the data; or the writing of the article and the decision to submit it for publication. Laura Laslett is supported by a National Health and Medical Research Council of Australia Early Career Fellowship (1070586). Graeme Jones is supported by a NHMRC Practitioner Fellowship (1023222).Peer reviewedPostprin

Non-Coding RNA Prediction and Verification in Saccharomyces cerevisiae

Non-coding RNA (ncRNA) play an important and varied role in cellular function. A significant amount of research has been devoted to computational prediction of these genes from genomic sequence, but the ability to do so has remained elusive due to a lack of apparent genomic features. In this work, thermodynamic stability of ncRNA structural elements, as summarized in a Z-score, is used to predict ncRNA in the yeast Saccharomyces cerevisiae. This analysis was coupled with comparative genomics to search for ncRNA genes on chromosome six of S. cerevisiae and S. bayanus. Sets of positive and negative control genes were evaluated to determine the efficacy of thermodynamic stability for discriminating ncRNA from background sequence. The effect of window sizes and step sizes on the sensitivity of ncRNA identification was also explored. Non-coding RNA gene candidates, common to both S. cerevisiae and S. bayanus, were verified using northern blot analysis, rapid amplification of cDNA ends (RACE), and publicly available cDNA library data. Four ncRNA transcripts are well supported by experimental data (RUF10, RUF11, RUF12, RUF13), while one additional putative ncRNA transcript is well supported but the data are not entirely conclusive. Six candidates appear to be structural elements in 5′ or 3′ untranslated regions of annotated protein-coding genes. This work shows that thermodynamic stability, coupled with comparative genomics, can be used to predict ncRNA with significant structural elements

A Randomized Trial of a Brace for Patellofemoral Osteoarthritis Targeting Knee Pain and Bone Marrow Lesions.

Objective Braces used to treat (PF) osteoarthritis (OA) may reduce contact stress across the PF joint. We hypothesised that in PF OA, braces would decrease knee pain and shrink PF bone marrow lesions (BMLs). Methods Eligible subjects had painful PF OA. Subjects were randomly allocated to brace or no brace for 6 weeks. Knee MRIs were acquired at baseline and 6 weeks. We measured BMLs on post-contrast fat suppressed sagittal and proton density weighted axial images. The primary symptom outcome was change in pain at 6 weeks during a preselected painful activity, and the primary structural outcome was BML volume change in the PF joint. Analyses used multiple linear regression. Results We randomised 126 subjects aged 40–70 years (mean age 55.5  years; 72 females (57.1%)). Mean nominated visual analogue scale (0–10 cm) pain score at baseline was 6.5 cm. 94 knees (75%) had PF BMLs at baseline. Subjects wore the brace for a mean of 7.4 h/day. 6 subjects withdrew during the trial. After accounting for baseline values, the brace group had lower knee pain than the control group at 6 weeks (difference between groups −1.3 cm, 95% CI −2.0 to −0.7; p<0.001) and reduced PF BML volume (difference −490.6 mm3, 95% CI −929.5 to −51.7; p=0.03) but not tibiofemoral volume (difference −53.9 mm3, 95% CI −625.9 to 518.2; p=0.85). Conclusions A PF brace reduces BML volume in the targeted compartment of the knee, and relieves knee pain

Plio-Pleistocene exhumation of the eastern Himalayan syntaxis and its domal ‘pop-up’

The eastern termination of the Himalayan orogen forms a structural syntaxis that is characterised by young (from 10 to &lt; 1 Ma) mineral growth and cooling ages that document Late Miocene to Pleistocene structural, metamorphic, igneous and exhumation events. This region is a steep antiformal and in part domal structure that folds the suture zone between the Indian and Asian plates. It is dissected by the Yarlung Tsangpo, one of the major rivers of the eastern Himalayan–Tibet region, which becomes the Brahmaputra River in the Indian foreland basin before emptying into the Bay of Bengal. Exceptionally high relief and one of the deepest gorges on Earth have developed where the river's tortuous route crosses the Namche Barwa–Gyala Peri massif (&gt; 7 km in elevation) in the core of the syntaxis. Very high erosion rates documented in sediment downstream of the gorge at the foot of the Himalaya contribute ~ 50% of total detritus to the sediment load of the Brahmaputra. The initiation of very high rates of exhumation has been attributed either to the extreme erosive power of a river flowing across a deforming indentor corner and the associated positive feedback, or to the geometry of the Indian plate indentor, with the corner being thrust beneath the Asian plate resulting in buckling which accommodates shortening; both processes may be important. The northern third of the syntaxis corresponds to a steep domal ‘pop-up’ structure bounded by the India–Asia suture on three sides and a thrust zone to the south. Within the dome, Greater Himalaya rocks equilibrated at ~ 800 °C and 25–30 km depth during the Miocene, with these conditions potentially persisting into the latest Miocene and possibly the Pliocene, with modest decompression prior to ~ 4 Ma. This domal ‘pop-up’ corresponds to the area of youngest bedrock ages on a wide variety of thermochronometers and geochronometers. In this paper we review the extensive scientific literature that has focused on the eastern syntaxis and provide new chronological data on its bedrock and erosion products to constrain the age of inception of the very rapid uplift and erosion. We then discuss its cause, with the ultimate aim to reconstruct the exhumation history of the syntaxis and discuss the tectonic context for its genesis. We use zircon and rutile U–Pb, white mica Ar–Ar and zircon fission track dating methods to extract age data from bedrock, Brahmaputra modern sediments (including an extensive compilation of modern detrital chronometry from the eastern Himalaya) and Neogene palaeo-Brahmaputra deposits of the Surma Basin (Bangladesh). Numerical modelling of heat flow and erosion is also used to model the path of rocks from peak metamorphic conditions of ~ 800 °C to &lt; 250 °C. Our new data include U–Pb bedrock rutile ages as young as 1.4 Ma from the Namche Barwa massif and 0.4 Ma from the river downstream of the syntaxis. Combined with existing data, our new data and heat flow modelling show that: i) the detrital age signature of the modern syntaxis is unique within the eastern Himalayan region; ii) the rocks within the domal pop-up were &gt; 575 ± 75 °C only 1–2 Myr ago; iii) the Neogene Surma Basin does not record evidence of the rise and erosion of the domal pop-up until latest Pliocene–Pleistocene time; iv) Pleistocene exhumation of the north-easternmost part of the syntaxis took place at rates of at least 4 km/Myr, with bedrock erosion of 12–21 km during the last 3 Ma; v) the inception of rapid syntaxial exhumation may have started as early as 7 Ma or as late as 3 Ma; and vi) the Yarlung Tsangpo is antecedent and subsequently distorted by the developing antiform. Together our data and modelling demonstrate that the domal pop-up with its exceptional erosion and topographic relief is likely a Pleistocene feature that overprinted earlier structural and metamorphic events typical of Himalayan evolution. Keywords: Eastern Himalayan syntaxis; Namche Barwa; Surma Basin; Yarlung Tsangpo–Brahmaputra; U–Pb rutile dating; Thermal modellin

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Efficacy and safety of plant-derived products for the treatment of osteoarthritis

Background: Plant-derived therapies are traditionally used as medicines, but they have generally not been studied with the same rigor as pharmaceutical agents. This review summarizes the use of plant-derived products for osteoarthritis. Methods: Sixty-three identified trials were summarized for pain, function, and safety outcomes using standardized mean differences (SMDs) and relative risks. Results: Plant-derived therapies are effective for treating pain compared to placebo, as assessed using visual analog scores and numerical rating scales (SMD, 1.08; 95% confidence interval [CI]: 0.72–1.44), or Western Ontario and McMaster University Osteoarthritis Index (WOMAC)/Knee injury and Osteoarthritis Outcome Score (KOOS) pain scales (SMD, 0.98; 95% CI: 0.62–1.35). Classes demonstrating overall efficacy in more than one trial for either visual analog scores or WOMAC pain included Boswellia serrata, capsaicin, and ginger; there was single-trial evidence of the efficacy of another nine agents. Plant-derived therapies have similar efficacy to an active comparator (SMD, 0.32; P=0.08; -0.08; P=0.14). Therapies are also effective for functional outcomes compared to placebo (SMD, 0.92; P<0.001). However, significant heterogeneity remains for all pain and function outcomes, indicating that the results need to be interpreted with caution. Risk of adverse events was similar to placebo (relative risk =1.13; P=0.1), but reduced compared to an active comparator (relative risk, 0.75; P<0.001). Conclusion: Plant-derived therapies may be efficacious in treating osteoarthritic pain and functional limitations, and they appear to be safer than other active therapies. However, quality trials and long-term data are lacking, and the number of trials for each therapy is limited. Comparisons would be assisted by trial standardization.20 page(s