The association between subgroups of MRI findings identified with latent class analysis and low back pain in 40-year old Danes

Background: Research into the clinical importance of spinal MRI findings in patients with low back pain (LBP) has primarily focused on single imaging findings, such as Modic changes or disc degeneration, and found only weak associations with the presence of pain. However, numerous MRI findings almost always co-exist in the lumbar spine and are often present at more than one lumbar level. It is possible that multiple MRI findings are more strongly associated with LBP than single MRI findings. Latent Class Analysis is a statistical method that has recently been tested and found useful for identifying latent classes (subgroups) of MRI findings within multivariable datasets. The purpose of this study was to investigate the association between subgroups of MRI findings and the presence of LBP in people from the general population. Methods: To identify subgroups of lumbar MRI findings with potential clinical relevance, Latent Class Analysis was initially performed on a clinical dataset of 631 patients seeking care for LBP. Subsequently, 412 participants in a general population cohort (the ‘Backs on Funen’ project) were statistically allocated to those existing subgroups by Latent Class Analysis, matching their MRI findings at a segmental level. The subgroups containing MRI findings from the general population were then organised into hypothetical pathways of degeneration and the association between subgroups in the pathways and the presence of LBP was tested using exact logistic regression. Results: Six subgroups were identified in the clinical dataset and the data from the general population cohort fitted the subgroups well, with a median posterior probability of 93%–100%. These six subgroups described two pathways of increasing degeneration on upper (L1-L3) and lower (L4-L5) lumbar levels. An association with LBP was found for the subgroups describing severe and multiple degenerative MRI findings at the lower lumbar levels but none of the other subgroups were associated with LBP

The GRONORUN 2 study: effectiveness of a preconditioning program on preventing running related injuries in novice runners. The design of a randomized controlled trial

Background: Distance running is a popular recreational exercise. It is a beneficial activity for health and well being. However, running may also cause injuries, especially of the lower extremities. In literature there is no agreement what intrinsic and extrinsic factors cause running related injuries (RRIs). In theory, most RRIs are elicited by training errors, this too much, too soon. In a preconditioning program runners can adapt more gradually to the high mechanical loads of running and will be less susceptible to RRIs. In this study the effectiveness of a 4-week preconditioning program on the incidence of RRIs in novice runners prior to a training program will be studied. Methods/Design: The GRONORUN 2 (Groningen Novice Running) study is a two arm randomized controlled trial studying the effect of a 4-week preconditioning (PRECON) program in a group of novice runners. All participants wanted to train for the recreational Groningen 4-Mile running event. The PRECON group started a 4-week preconditioning program with walking and hopping exercises 4 weeks before the start of the training program. The control (CON) and PRECON group started a frequently used 9-week training program in preparation for the Groningen 4-Mile running event. During the follow up period participants registered their running exposure, other sporting activities and running related injuries in an Internet based running log. The primary outcome measure was the number of RRIs. RRI was defined as a musculoskeletal ailment or complaint of the lower extremities or back causing a restriction on running for at least three training sessions. Discussion: The GRONORUN 2 study will add important information to the existing running science. The concept of preconditioning is easy to implement in existing training programs and will hopefully prevent RRIs especially in novice runners

Integrated method for quantitative morphometry and oxygen transport modelling in striated muscle

Identifying structural limitations in O2 transport is primarily restricted by current methods employed to characterise the nature of physiological remodelling. Inadequate resolution or breadth of available data has impaired development of routine diagnostic protocols and effective therapeutic strategies. Understanding O2 transport within striated muscle faces major challenges, most notably in quantifying how well individual fibres are supplied by the microcirculation, which has necessitated exploring tissue O2 supply using theoretical modelling of diffusive exchange. Having identified capillary domains as a suitable model for the description of local O2 supply, and requiring less computation than numerically calculating the trapping regions that are supplied by each capillary via biophysical transport models, we sought to design a high throughput method for histological analysis. We present an integrated package that identifies optimal protocols for identification of important input elements, processing of digitised images with semi-automated routines, and incorporation of these data into a mathematical modelling framework with computed output visualised as the tissue partial pressure of O2 (PO2) distribution across a biopsy sample. Worked examples are provided using muscle samples from experiments involving rats and humans

Solving 1d plasmas and 2d boundary problems using Jack polynomials and functional relations

The general one-dimensional ``log-sine'' gas is defined by restricting the positive and negative charges of a two-dimensional Coulomb gas to live on a circle. Depending on charge constraints, this problem is equivalent to different boundary field theories. We study the electrically neutral case, which is equivalent to a two-dimensional free boson with an impurity cosine potential. We use two different methods: a perturbative one based on Jack symmetric functions, and a non-perturbative one based on the thermodynamic Bethe ansatz and functional relations. The first method allows us to compute explicitly all coefficients in the virial expansion of the free energy and the experimentally-measurable conductance. Some results for correlation functions are also presented. The second method provides in particular a surprising fluctuation-dissipation relation between the free energy and the conductance.Comment: 19 page

Chiral and herringbone symmetry breaking in water-surface monolayers

We report the observation from monolayers of eicosanoic acid in the L′2 phase of three distinct out-of-plane first-order diffraction peaks, indicating molecular tilt in a nonsymmetry direction and hence the absence of mirror symmetry. At lower pressures the molecules tilt in the direction of their nearest neighbors. In this region we find a structural transition, which we tentatively identify as the rotator-herringbone transition L2d−L2h

A randomised phase II multicentre trial of irinotecan (CPT-11) using four different schedules in patients with metastatic colorectal cancer

The purpose of this phase II trial was to compare the efficacy, safety and pharmacokinetics of four irinotecan schedules for the treatment of metastatic colorectal cancer. In total, 174 5-fluorouracil pretreated patients were randomised to: arm A (n=41), 350 mg m(-2) irinotecan as a 90-min i.v. infusion q3 weeks; arm B (n=38), 125 mg m(-2) irinotecan as a 90-min i.v. infusion weekly x 4 weeks q6 weeks; arm C (n=46), 250 mg m(-2) irinotecan as a 90-min i.v. infusion q2 weeks; or arm D (n=49), 10 mg m(-2) day(-1) irinotecan as a 14-day continuous infusion q3 weeks. No significant differences in efficacy across the four arms were observed, although a shorter time to treatment failure was noted for arm D (1.7 months; P=0.02). Overall response rates were in the range 5-11%. Secondary end points included median survival (6.4-9.4 months), and time to progression (2.7-3.8 months) and treatment failure (1.7-3.2 months). Similarly, there were no significant differences in the incidence of grade 3-4 toxicities, although the toxicity profile between arms A, B, and C and D did differ. Generally, significantly less haematologic toxicity, alopecia and cholinergic syndrome were observed in arm D; however, there was a trend for increased gastrointestinal toxicity. Irinotecan is an effective and safe second-line treatment for colorectal cancer. The schedules examined yielded equivalent results, indicating that there is no advantage of the prolonged vs short infusion schedule

ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: A comprehensive analysis from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas

<b>Objective</b> <i>ABCB1</i> encodes the multi-drug efflux pump P-glycoprotein (P-gp) and has been implicated in multi-drug resistance. We comprehensively evaluated this gene and flanking regions for an association with clinical outcome in epithelial ovarian cancer (EOC).<p></p> <b>Methods</b> The best candidates from fine-mapping analysis of 21 <i>ABCB1</i> SNPs tagging C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642) were analysed in 4616 European invasive EOC patients from thirteen Ovarian Cancer Association Consortium (OCAC) studies and The Cancer Genome Atlas (TCGA). Additionally we analysed 1,562 imputed SNPs around ABCB1 in patients receiving cytoreductive surgery and either ‘standard’ first-line paclitaxel–carboplatin chemotherapy (n = 1158) or any first-line chemotherapy regimen (n = 2867). We also evaluated ABCB1 expression in primary tumours from 143 EOC patients.<p></p> <b>Result</b> Fine-mapping revealed that rs1128503, rs2032582, and rs1045642 were the best candidates in optimally debulked patients. However, we observed no significant association between any SNP and either progression-free survival or overall survival in analysis of data from 14 studies. There was a marginal association between rs1128503 and overall survival in patients with nil residual disease (HR 0.88, 95% CI 0.77–1.01; p = 0.07). In contrast, <i>ABCB1</i> expression in the primary tumour may confer worse prognosis in patients with sub-optimally debulked tumours.<p></p> <b>Conclusion</b> Our study represents the largest analysis of <i>ABCB1</i> SNPs and EOC progression and survival to date, but has not identified additional signals, or validated reported associations with progression-free survival for rs1128503, rs2032582, and rs1045642. However, we cannot rule out the possibility of a subtle effect of rs1128503, or other SNPs linked to it, on overall survival.<p></p&gt

Determination of the b quark mass at the M_Z scale with the DELPHI detector at LEP

An experimental study of the normalized three-jet rate of b quark events with respect to light quarks events (light= \ell \equiv u,d,s) has been performed using the CAMBRIDGE and DURHAM jet algorithms. The data used were collected by the DELPHI experiment at LEP on the Z peak from 1994 to 2000. The results are found to agree with theoretical predictions treating mass corrections at next-to-leading order. Measurements of the b quark mass have also been performed for both the b pole mass: M_b and the b running mass: m_b(M_Z). Data are found to be better described when using the running mass. The measurement yields: m_b(M_Z) = 2.85 +/- 0.18 (stat) +/- 0.13 (exp) +/- 0.19 (had) +/- 0.12 (theo) GeV/c^2 for the CAMBRIDGE algorithm. This result is the most precise measurement of the b mass derived from a high energy process. When compared to other b mass determinations by experiments at lower energy scales, this value agrees with the prediction of Quantum Chromodynamics for the energy evolution of the running mass. The mass measurement is equivalent to a test of the flavour independence of the strong coupling constant with an accuracy of 7 permil.Comment: 24 pages, 10 figures, Accepted by Eur. Phys. J.

An exploration of parents’ preferences for foot care in juvenile idiopathic arthritis: a possible role for the discrete choice experiment

Background: An increased awareness of patients’ and parents’ care preferences regarding foot care is desirable from a clinical perspective as such information may be utilised to optimise care delivery. The aim of this study was to examine parents’ preferences for, and valuations of foot care and foot-related outcomes in juvenile idiopathic arthritis (JIA).<p></p> Methods: A discrete choice experiment (DCE) incorporating willingness-to-pay (WTP) questions was conducted by surveying 42 parents of children with JIA who were enrolled in a randomised-controlled trial of multidisciplinary foot care at a single UK paediatric rheumatology outpatients department. Attributes explored were: levels of pain; mobility; ability to perform activities of daily living (ADL); waiting time; referral route; and footwear. The DCE was administered at trial baseline. DCE data were analysed using a multinomial-logit-regression model to estimate preferences and relative importance of attributes of foot care. A stated-preference WTP question was presented to estimate parents’ monetary valuation of health and service improvements.<p></p> Results: Every attribute in the DCE was statistically significant (p < 0.01) except that of cost (p = 0.118), suggesting that all attributes, except cost, have an impact on parents’ preferences for foot care for their child. The magnitudes of the coefficients indicate that the strength of preference for each attribute was (in descending order): improved ability to perform ADL, reductions in foot pain, improved mobility, improved ability to wear desired footwear, multidisciplinary foot care route, and reduced waiting time. Parents’ estimated mean annual WTP for a multidisciplinary foot care service was £1,119.05.<p></p> Conclusions: In terms of foot care service provision for children with JIA, parents appear to prefer improvements in health outcomes over non-health outcomes and service process attributes. Cost was relatively less important than other attributes suggesting that it does not appear to impact on parents’ preferences.<p></p&gt