2,250 research outputs found

    A Solution Merging Heuristic for the Steiner Problem in Graphs Using Tree Decompositions

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    Fixed parameter tractable algorithms for bounded treewidth are known to exist for a wide class of graph optimization problems. While most research in this area has been focused on exact algorithms, it is hard to find decompositions of treewidth sufficiently small to make these al- gorithms fast enough for practical use. Consequently, tree decomposition based algorithms have limited applicability to large scale optimization. However, by first reducing the input graph so that a small width tree decomposition can be found, we can harness the power of tree decomposi- tion based techniques in a heuristic algorithm, usable on graphs of much larger treewidth than would be tractable to solve exactly. We propose a solution merging heuristic to the Steiner Tree Problem that applies this idea. Standard local search heuristics provide a natural way to generate subgraphs with lower treewidth than the original instance, and subse- quently we extract an improved solution by solving the instance induced by this subgraph. As such the fixed parameter tractable algorithm be- comes an efficient tool for our solution merging heuristic. For a large class of sparse benchmark instances the algorithm is able to find small width tree decompositions on the union of generated solutions. Subsequently it can often improve on the generated solutions fast

    Acetabular labrum reconstruction with fresh meniscus allograft transplantation : validation in a preclinical canine model

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    "Acetabular labrum pathology is frequently diagnosed in young, active individuals. Methods of hip preservation emphasize recapitulation of labrum structure and function to re-establish joint health and mitigate the development of hip osteoarthritis (OA). Labrum reconstruction utilizing fresh, frozen tendon allograft has become a popular option based on good short-term outcomes, however, failure rates are ~24%. Meniscus allograft has demonstrated early success as an alternative due to similarities in geometry, tissue composition, and metabolic profile when compared to acetabular labrum tissue. Healing of the fresh (viable) meniscus allografts transplantation (MAT) has not been well characterized."--Introduction

    Prediction of Lifetime and 10-Year Risk of Cancer in Individual Patients With Established Cardiovascular Disease

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    BACKGROUND: Cardiovascular disease (CVD) and cancer share many common risk factors; patients with CVD also may be at risk of developing cancer. OBJECTIVES: The aim of this study was to derive and externally validate prediction models for the estimation of lifetime and 10-year risk for total, colorectal, and lung cancer in patients with established CVD. METHODS: Data from patients with established CVD from the UCC-SMART cohort (N ÂĽ 7,280) were used for model development, and from the CANTOS trial (N ÂĽ 9,322) for model validation. Predictors were selected based on previously published cancer risk scores, clinical availability, and presence in the derivation dataset. Fine and Gray competing risk-adjusted lifetime models were developed for the outcomes total, colorectal, and lung cancer. RESULTS: Selected predictors were age, sex, smoking, weight, height, alcohol use, antiplatelet use, diabetes, and C-reactive protein. External calibration for the 4-year risk of lung, colorectal, and total cancer was reasonable in our models, as was discrimination with C-statistics of 0.74, 0.64, and 0.63, respectively. Median predicted lifetime and 10-year risks in CANTOS were 26% (range 1% to 52%) and 13% (range 1% to 31%) for total cancer; 4% (range 0% to 13%) and 2% (range 0% to 6%) for colorectal cancer; and 5% (range 0% to 37%) and 2% (range 0% to 24%) for lung cancer. CONCLUSIONS: Lifetime and 10-year risk of total, colorectal, and lung cancer can be estimated reasonably well in patients with established CVD with readily available clinical predictors. With additional study, these tools could be used in clinical practice to further aid in the emphasis of healthy lifestyle changes and to guide thresholds for targeted diagnostics and screening

    The value of baseline 18F-sodium fluoride and 18F-choline PET activity for identifying responders to radium-223 treatment in castration-resistant prostate cancer bone metastases.

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    OBJECTIVES: To investigate whether baseline 18F-sodium fluoride (NaF) and 18F-choline PET activity is associated with metastatic castration-resistant prostate cancer (mCRPC) global and individual bone metastases' DWI MR imaging response to radium-223 treatment. METHODS: Thirty-six bone-only mCRPC patients were prospectively recruited from three centers. Whole-body (WB)-MRI with DWI and 18F-NaF and 18F-choline PET/CT were performed at therapy baseline and 8-week intervals. In each patient, bone disease median global (g)ADC change between baseline and follow-up was calculated. Additionally, up to five bone target lesions per patient were delineated and individual median ADC change recorded. An ADC increase > 30% defined response per-patient and per-lesion. For the same targets, baseline 18F-NaF and 18F-choline PET SUVmax were recorded. Mean SUVmax across patient targets was correlated with gADC change and lesion SUVmax with per-lesion ADC change. RESULTS: A total of 133 lesions in 36 patients (14 responders) were analyzed. 18F-NaF PET per-patient mean SUVmax was significantly higher in responders (median = 56.0 versus 38.7 in non-responders; p = 0.008), with positive correlation between SUVmax and gADC increase (rho = 0.42; p = 0.015). A 48.7 SUVmax threshold identified responders with 77% sensitivity and 75% specificity. Baseline 18F-NaF PET per-lesion SUVmax was higher in responding metastases (median = 51.6 versus 31.8 in non-responding metastases; p = 0.001), with positive correlation between baseline lesion SUVmax and ADC increase (rho = 0.39; p < 0.001). A 36.8 SUVmax threshold yielded 72% sensitivity and 63% specificity. No significant association was found between baseline 18F-choline PET SUVmax and ADC response on a per-patient (p = 0.164) or per-lesion basis (p = 0.921). CONCLUSION: 18F-NaF PET baseline SUVmax of target mCRPC bone disease showed significant association with response to radium-223 defined by ADC change. CLINICAL RELEVANCE STATEMENT: 18F-sodium fluoride PET/CT baseline maximum SUV of castration-resistant prostate cancer bone metastases could be used as a predictive biomarker for response to radium-223 therapy. KEY POINTS: • 18F-sodium fluoride PET baseline SUVmax of castration-resistant prostate cancer bone metastases showed significant association with response to radium-223. • Baseline 18F-sodium fluoride PET can improve patient selection for radium-223 therapy. • Change in whole-body DWI parameters can be used for response correlation with baseline 18F-sodium fluoride PET SUVmax in castration-resistant prostate cancer bone metastases

    Using assignment data to analyse a blended information literacy intervention: a quantitative approach

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    This research sought to determine whether a blended information literacy learning and teaching intervention could statistically significantly enhance undergraduates’ information discernment compared to standard face-to-face delivery. A mixture of face-to-face and online activities, including online social media learning, was used. Three interventions were designed to develop the information literacies of first-year undergraduates studying Sport and Exercise at Staffordshire University and focused on one aspect of information literacy: the ability to evaluate source material effectively. An analysis was devised where written evaluations of found information for an assessment were converted into numerical scores and then measured statistically. This helped to evaluate the efficacy of the interventions and provided data for further analysis. An insight into how the information literacy pedagogical intervention and the cognitive processes involved in enabling participants to interact critically with information is provided. The intervention which incorporated social media learning proved to be the most successful learning and teaching approach. The data indicated that undergraduate students’ information literacy can be developed. However, additional long-term data is required to establish whether this intervention would have a lasting impact

    Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy

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    Human mutations that truncate the massive sarcomere protein titin [TTN-truncating variants (TTNtvs)] are the most common genetic cause for dilated cardiomyopathy (DCM), a major cause of heart failure and premature death. Here we show that cardiac microtissues engineered from human induced pluripotent stem (iPS) cells are a powerful system for evaluating the pathogenicity of titin gene variants. We found that certain missense mutations, like TTNtvs, diminish contractile performance and are pathogenic. By combining functional analyses with RNA sequencing, we explain why truncations in the A-band domain of TTN cause DCM, whereas truncations in the I band are better tolerated. Finally, we demonstrate that mutant titin protein in iPS cell-derived cardiomyocytes results in sarcomere insufficiency, impaired responses to mechanical and {beta}-adrenergic stress, and attenuated growth factor and cell signaling activation. Our findings indicate that titin mutations cause DCM by disrupting critical linkages between sarcomerogenesis and adaptive remodeling

    K30, H150, and H168 Are Essential Residues for Coordinating Pyridoxal 5′-Phosphate of O-Acetylserine Sulfhydrylase from Acidithiobacillus ferrooxidans

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    O-acetylserine sulfhydrylase (OASS) is a key enzyme involved in the pathway of the cysteine biosynthesis. The gene of OASS from Acidithiobacillus ferrooxidans ATCC 23270 was cloned and expressed in E. coli, the soluble protein was purified by one-step affinity chromatography to apparent homogeneity. Colors and UV–vis scanning results of the recombinant protein confirmed that it was a pyridoxal 5′-phosphate (PLP)-containing protein. Sequence alignment and site-directed mutation of the enzyme revealed that the cofactor PLP is covalently bound in Schiff base linkage with K30, as well as the two residues H150 and H168 were the crucial residues for PLP binding and stabilization

    Axillary silicone lymphadenopathy presenting with a lump and altered sensation in the breast: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Silicone lymphadenopathy is a rare but recognised complication of procedures involving the use of silicone. It has a poorly understood mechanism but is thought to occur following the transportation of silicone particles from silicone-containing prostheses to lymph nodes by macrophages.</p> <p>Case presentation</p> <p>We report of a case involving a 35-year-old woman who presented to the breast clinic with a breast lump and altered sensation below her left nipple 5 years after bilateral cosmetic breast augmentations. A small lump was detected inferior to the nipple but clinical examination and initial ultrasound investigation showed both implants to be intact. However, mammography and magnetic resonance imaging of both breasts revealed both intracapsular and extracapsular rupture of the left breast prosthesis. The patient went on to develop a flu-like illness and tender lumps in the left axilla and right mastoid regions. An excision biopsy of the left axillary lesion and replacement of the ruptured implant was performed. Subsequent histological analysis showed that the axillary lump was a lymph node containing large amounts of silicone.</p> <p>Conclusion</p> <p>The exclusion of malignancy remains the priority when dealing with lumps in the breast or axilla. Silicone lymphadenopathy should however be considered as a differential diagnosis in patients in whom silicone prostheses are present.</p
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