A traffic light grading system of hip dysplasia to predict the success of arthroscopic hip surgery

Background: The role of hip arthroscopy in dysplasia is controversial. Purpose: Determine the 7-year joint preservation rate following hip arthroscopy in hip dysplasia and identify anatomical and intra-operative features that predict success of hip preservation with arthroscopic surgery allowing formulation of an evidence-based classification. Study Design: Cohort Study; Level of evidence: 3 Methods: Between 2008 and 2013, 111 hips with dysplastic features [acetabular index (AI) > 10° and/or centre-edge angle (CEA) <25°] having undergone an arthroscopy were identified. Clinical, radiological and operative findings and type of procedure performed were reviewed. Radiographic evaluations of the operated hip [acetabular index (AI), centre-edge angle (CEA), extrusion index] were performed. Outcome measures included whether the hip was preserved at follow-up, pre- and post-operative NAHS and HOOS scores. We calculated AI and CEA factored (AIf and CEAf respectively) by a measure of articular wear as follows: AIf = AI x (number of UCL wear zones +1) CEAf = CEA / (number of UCL zones + 1) A contour plot of the resulting probability value of failure for every combination of AIf and CEAf allowed for the determination of the zones with the lowest and highest incidence of failure to preserve the hip respectively. Results: The mean AI and CEA were 7.8° and 18.0°, respectively. At a mean follow-up of 4.4 years, 33 hips had failed requiring a hip arthroplasty. The 7- year joint survival was 68%. The mean improvement in NAHS and HOOS were 7.8 and 23 points respectively. The zone with the greatest chance of joint preservation (odds ratio: 10, p<0.001) was AIf: 0 – 15 and CEAf: 15 – 25 (Green Zone); on the contrary the zone with the greatest chance of failure (odds ratio: 10, p<0.001) was AIf: 20 – 100 and CEAf : 0 – 10 (Red Zone). Conclusion: Overall, the 7- year hip survival in hip dysplasia appears inferior compared to reports of Femoro-Acetabular Impingement cases. Hip arthroscopy is associated with excellent chance of hip preservation in mild (Green Zone) dysplasia (AI< 15° & CEA: 15 – 25°) and no (or little) articular wear. Hip arthroscopy should not be performed in cases with severe (Red Zone) dysplasia (AI> 20° & CEA< 10°)

Revisit Sparse Polynomial Interpolation based on Randomized Kronecker Substitution

In this paper, a new reduction based interpolation algorithm for black-box multivariate polynomials over finite fields is given. The method is based on two main ingredients. A new Monte Carlo method is given to reduce black-box multivariate polynomial interpolation to black-box univariate polynomial interpolation over any ring. The reduction algorithm leads to multivariate interpolation algorithms with better or the same complexities most cases when combining with various univariate interpolation algorithms. We also propose a modified univariate Ben-or and Tiwarri algorithm over the finite field, which has better total complexity than the Lagrange interpolation algorithm. Combining our reduction method and the modified univariate Ben-or and Tiwarri algorithm, we give a Monte Carlo multivariate interpolation algorithm, which has better total complexity in most cases for sparse interpolation of black-box polynomial over finite fields

Glioblastoma stem cells induce quiescence in surrounding neural stem cells via Notch signalling.

There is increasing evidence demonstrating that adult neural stem cells (NSCs) are a cell of origin of glioblastoma. Here we analyzed the interaction between transformed and wild-type NSCs isolated from the adult mouse subventricular zone niche. We found that transformed NSCs are refractory to quiescence-inducing signals. Unexpectedly, we also demonstrated that these cells induce quiescence in surrounding wild-type NSCs in a cell–cell contact and Notch signaling-dependent manner. Our findings therefore suggest that oncogenic mutations are propagated in the stem cell niche not just through cell-intrinsic advantages, but also by outcompeting neighboring stem cells through repression of their proliferation

EVALUATION OF AN END-TO-END RADIOTHERAPY TREATMENT PLANNING PIPELINE FOR PROSTATE CANCER

Radiation treatment planning is a crucial and time-intensive process in radiation therapy. This planning involves carefully designing a treatment regimen tailored to a patient’s specific condition, including the type, location, and size of the tumor with reference to surrounding healthy tissues. For prostate cancer, this tumor may be either local, locally advanced with extracapsular involvement, or extend into the pelvic lymph node chain. Automating essential parts of this process would allow for the rapid development of effective treatment plans and better plan optimization to enhance tumor control for better outcomes. The first objective of this work, to automate the treatment planning process, was the automatic segmentation of critical structures. Delineation of both target and normal tissue structures was necessary to establish the foundation for identifying where radiation must be delivered and what should be spared from excess radiation. Deep learning segmentation models were developed from retrospective CT simulation imaging data and clinical contours to delineate intact, postoperative, and nodal treatment structures for prostate cancer to accomplish this objective. Quality contours were extracted per established contouring guidelines in the literature. Model refinement on a holdout fine-tune dataset was used to verify model contours before quantitative and qualitative evaluation on the holdout test set. Predicted contours resulted in contours comparable in quantitative Dice-Similarity-Coefficient (DSC) and 95% Hausdorff Distance (HD95) to proposed models in literature and clinically usable contours with no more than minor edits upon physician review. The second objective was the automation of Volumetric Modulated Arc Therapy (VMAT) planning for a breadth of prostate treatment scenarios. Development of VMAT plans for intact, postoperative, and nodal involvement treatment cases was necessary for the sequence in daily treatment delivery and the prospective distribution of radiation dose to target and normal tissues. To accomplish this objective, knowledge-based planning models were separately developed to estimate patient-specific DVHs to guide plan optimization for radiation delivery. These two models were then used in this work for end-to-end testing of cases with and without lymph node involvement, including determining if the prostate target is intact or postoperative with or without treatment devices such as hydrogel spacers and rectal balloons. A sequence of iterative optimization runs was created to ensure hotspot reduction and target conformality. The findings demonstrated that plans developed from automatically generated contours were clinically usable with minor edits for intact and postoperative treatments without lymph node involvement. For treatments with lymph node involvement, dose constraints were met for a select set of cases without excessive rectum curvature or excessive bladder descension into the postoperative treatment bed. When comparing auto-segmented to clinical contours, clinical contours experienced similar pass rates as those achieved by auto-segmented contours

Estimating Discrete Markov Models From Various Incomplete Data Schemes

The parameters of a discrete stationary Markov model are transition probabilities between states. Traditionally, data consist in sequences of observed states for a given number of individuals over the whole observation period. In such a case, the estimation of transition probabilities is straightforwardly made by counting one-step moves from a given state to another. In many real-life problems, however, the inference is much more difficult as state sequences are not fully observed, namely the state of each individual is known only for some given values of the time variable. A review of the problem is given, focusing on Monte Carlo Markov Chain (MCMC) algorithms to perform Bayesian inference and evaluate posterior distributions of the transition probabilities in this missing-data framework. Leaning on the dependence between the rows of the transition matrix, an adaptive MCMC mechanism accelerating the classical Metropolis-Hastings algorithm is then proposed and empirically studied.Comment: 26 pages - preprint accepted in 20th February 2012 for publication in Computational Statistics and Data Analysis (please cite the journal's paper

Uniform Bahadur Representation for Nonparametric Censored Quantile Regression: A Redistribution-of-Mass Approach

Censored quantile regressions have received a great deal of attention in the literature. In a linear setup, recent research has found that an estimator based on the idea of “redistribution-of-mass” in Efron (1967, Proceedings of the Fifth Berkeley Symposium on Mathematical Statistics and Probability, vol. 4, pp. 831–853, University of California Press) has better numerical performance than other available methods. In this paper, this idea is combined with the local polynomial kernel smoothing for nonparametric quantile regression of censored data. We derive the uniform Bahadur representation for the estimator and, more importantly, give theoretical justification for its improved efficiency over existing estimation methods. We include an example to illustrate the usefulness of such a uniform representation in the context of sufficient dimension reduction in regression analysis. Finally, simulations are used to investigate the finite sample performance of the new estimator

Sustained mucosal colonization and fecal metabolic dysfunction by Bacteroides associates with fecal microbial transplant failure in ulcerative colitis patients.

Fecal microbial transplantation (FMT) offers promise for treating ulcerative colitis (UC), though the mechanisms underlying treatment failure are unknown. This study harnessed longitudinally collected colonic biopsies (n = 38) and fecal samples (n = 179) from 19 adults with mild-to-moderate UC undergoing serial FMT in which antimicrobial pre-treatment and delivery mode (capsules versus enema) were assessed for clinical response (≥ 3 points decrease from the pre-treatment Mayo score). Colonic biopsies underwent dual RNA-Seq; fecal samples underwent parallel 16S rRNA and shotgun metagenomic sequencing as well as untargeted metabolomic analyses. Pre-FMT, the colonic mucosa of non-responsive (NR) patients harbored an increased burden of bacteria, including Bacteroides, that expressed more antimicrobial resistance genes compared to responsive (R) patients. NR patients also exhibited muted mucosal expression of innate immune antimicrobial response genes. Post-FMT, NR and R fecal microbiomes and metabolomes exhibited significant divergence. NR metabolomes had elevated concentrations of immunostimulatory compounds including sphingomyelins, lysophospholipids and taurine. NR fecal microbiomes were enriched for Bacteroides fragilis and Bacteroides salyersiae strains that encoded genes capable of taurine production. These findings suggest that both effective mucosal microbial clearance and reintroduction of bacteria that reshape luminal metabolism associate with FMT success and that persistent mucosal and fecal colonization by antimicrobial-resistant Bacteroides species may contribute to FMT failure

A traffic light grading system of hip dysplasia to predict the success of arthroscopic hip surgery

Background: The role of hip arthroscopic surgery in dysplasia is controversial. Purpose: To determine the 7-year joint preservation rate after hip arthroscopic surgery in hip dysplasia and identify anatomic and intraoperative features that predict the success of hip preservation with arthroscopic surgery, allowing the formulation of an evidence-based classification system. Study Design: Case-control study; Level of evidence, 3. Methods: Between 2008 and 2013, 111 hips with dysplastic features (acetabular index [AI] &gt;10° and/or lateral center-edge angle [LCEA] &lt;25°) that underwent arthroscopic surgery were identified. Clinical, radiological, and operative findings and the type of procedure performed were reviewed. Radiographic evaluations of the operated hip (AI, LCEA, extrusion index) were performed. Outcome measures included whether the hip was preserved (ie, did not require arthroplasty) at follow-up and the preoperative and postoperative Non-Arthritic Hip Score (NAHS) and Hip disability and Osteoarthritis Outcome Score (HOOS). The AI and LCEA were calculated, factored by a measure of articular wear (AIf and LCEAf, respectively), according to the University College Hospital, London (UCL) grading system as follows: AIf = AI × (number of UCL wear zones + 1), and LCEAf = LCEA / (number of UCL wear zones + 1). A contour plot of the resulting probability value of failure for every combination of AIf and LCEAf allowed for the determination of the zones with the lowest and highest incidences of failure to preserve the hip. Results: The mean AI and LCEA were 9.8° and 18.0°, respectively. At a mean follow-up of 4.5 years (range, 0.4-8.3 years), 33 hips had failed, requiring hip arthroplasty. The 7-year joint survival rate was 68%. The mean improvements in the NAHS and HOOS were 11 ( P = .001) and 22.8 ( P &lt; .001) points, respectively. The zone with the greatest chance of joint preservation (odds ratio, 10; P &lt; .001) was the green zone, with an AIf of 0° to 15° and an LCEAf of 15° to 25°; in contrast, the zone with the greatest chance of failure (odds ratio, 10; P &lt; .001) was the red zone, with an AIf of 20° to 100° and an LCEAf of 0° to 10°. Conclusion: Overall, the 7-year hip survival rate in hip dysplasia appears inferior compared with that reported in femoroacetabular impingement (78%). Hip arthroscopic surgery is associated with an excellent chance of hip preservation in mild dysplasia (green zone: AI = 0°-15°, LCEA = 15°-25°) and no articular wear. The authors advise that the greatest caution should be used when considering arthroscopic options in cases of severe dysplasia (red zone: AI &gt;20° and/or LCEA &lt;10°). </jats:sec

The connecting health and technology study: A 6-month randomized controlled trial to improve nutrition behaviours using a mobile food record and text messaging support in young adults

© 2016 Kerr et al. Background: Early adulthood represents the transition to independent living which is a period when changes in diet and body weight are likely to occur. This presents an ideal time for health interventions to reduce the effect of health problems and risk factors for chronic disease in later life. As young adults are high users of mobile devices, interventions that use this technology may improve engagement. The Connecting Health and Technology study aimed to evaluate the effectiveness of tailored dietary feedback and weekly text messaging to improve dietary intake of fruit, vegetables and junk food over 6 months among a population-based sample of men and women (aged 18-30 years). Methods: A three-arm, parallel, randomized control trial was conducted. After baseline assessments, participants were randomized to one of three groups: A) dietary feedback and weekly text messages, B) dietary feedback only or C) control group. Dietary intake was assessed using a mobile food record App (mFR) where participants captured images of foods and beverages consumed over 4-days at baseline and post-intervention. The primary outcomes were changes in serves of fruits, vegetables, energy-dense nutrient-poor (EDNP) foods and sugar-sweetened beverages (SSB). The intervention effects were assessed using linear mixed effect models for change in food group serves. Results: Young adults (n = 247) were randomized to group A (n = 82), group B (n = 83), or group C (n = 82). Overall, no changes in food group serves for either intervention groups were observed. An unanticipated outcome was a mean weight reduction of 1.7 kg (P = .02) among the dietary feedback only. Men who received dietary feedback only, significantly reduced their serves of EDNP foods by a mean of 1.4 serves/day (P = .02). Women who received dietary feedback only significantly reduced their intake of SSB (P = .04) by an average of 0.2 serves/day compared with controls. Conclusions: Tailored dietary feedback only resulted in a decrease in EDNP foods in men and SSB in women, together with a reduction in body weight. Using a mobile food record for dietary assessment and tailored feedback has great potential for future health promotion interventions targeting diet and weight in young adults. Trial Registration: Australian Clinical Trials Registry Registration number: ACTRN12612000250831

Evading innate immunity in nonviral mRNA delivery : don't shoot the messenger

In de field of non-viral gene therapy, in vitro transcribed (IVT) mRNA has emerged as a promising tool for the delivery of genetic information. Over the past few years it has become widely known the introduction of IVT mRNA into mammalian cells elicits an innate immune response which has favored mRNA use towards immunotherapeutic vaccination strategies. However, for non-immunotherapy related applications this intrinsic immune-stimulatory activity directly interferes with the aimed therapeutic outcome, as it can seriously compromise the expression of the desired protein. This review presents an overview of the immune-related obstacles that limit mRNA advance for non-immunotherapy related applications