Structure of (22\u3cem\u3eS\u3c/em\u3e)-3\u3cem\u3eβ\u3c/em\u3e-Acetoxy-20-(3-isopropylisoxazolin-5-yl)-4,4,14 \u3cem\u3eα\u3c/em\u3e-trimethylpregn-8(9)-ene

C32H51NO3, Mr = 497·7, orthorhombic, P212121, a = 7·577 (2), b = 10·510 (2), c = 35·399 (7) Å, V = 2819 (1) Å3, Z = 4, Dx = 1·173 g cm-3, λ (Mo Kα) = 0·71073 Å, μ = 0·69 cm-1, F(000) = 1096, T = 153 K, R = 0·0497 for 2235 observed reflections. The compound investigated is found to be a (22S)-epimer

ΔT-window neutron spectrometer

A high resolution neutron spectrometer making use of a ΔT-window filter for the analyser and time-of-flight technique for analysing incident neutron energy has been designed. The spectrometer will provide a continuously variable energy resolution ΔE from 40-50μeV at ~ 5230μeV. The range of energy transfer allowed is -1450μeV to +2950μeV and the range of wavevector transferQ allowed is 0.82-3.06 Å-1. Depending on the resolution used, the counting rates are expected to vary from 28-60 × 103 counts/hr if one assumes 10% isotropic elastic scattering from the sample

Efficacy and toxicity of SBRT in advanced hepatocellular carcinoma with portal vein tumor thrombosis — a retrospective study

BACKGROUND: The purpose of this study was to evaluate the outcome of stereotactic body radiation therapy (SBRT) in patients of unresectable hepatocellular carcinoma (HCC) complicated with portal vein tumor thrombosis (PVTT) who are also unsuitable for other locoregional therapies. MATERIALS AND METHODS: Between May 2018 and January 2020, twenty-nine patients with advanced unresectable HCCs, treated with SBRT, were enrolled in this retrospective audit. Patients of Child status A5-B7 and with healthy liver volume, ≥ 700 ccs were treated. Local control (LC), overall survival (OS), progression-free survival (PFS), PVTT opening rate, and effect of prognostic factors were analyzed. RESULTS: The median tumor diameter was 8.6 cm (5–14), and the median tumor volume was 275 cc (151–1196). The median SBRT dose prescription was 48 Gy in 6 fractions (32–50 Gy in 5–6 fractions). The median follow up was eight months (1–20), 1-year local control, progression-free survival, and overall survival were 95%, 53.4%, and 60%, respectively. Overall rate of grade III toxicity was less than 5%, and the most common toxicity was lymphocytopenia. Tumors of more than 350cc had worse OS and PFS when compared to tumors < 350 cc (median OS and PFS of tumors > 350 cc was 4 months and two months, p = .01 and .003, respectively). A total of fifteen patients progressed with the disease and the median time to progression was two months [1–4]. CONCLUSION: SBRT is safe and provides excellent local control in advanced HCC complicated with PVTT. The out of field failure pattern and time to failure in these patients highlights the need for adjuvant systemic therapy after completion of local treatment. Our data warrant the need for multimodality trials in this patient cohort

Efficiency of a novel non-monotonic segmented leaf sequence delivery of Varian MLC for non-split IMRT fields

AimDevelopment of bidirectional non-monotonic segmented leaf sequence (NSLS) MLC delivery technique compatible with Varian MLC for non-split IMRT fields reducing total monitor units (TotalMU) and the number of segments (NS) simultaneously and assessment of its efficiency using a plan scoring index (PSI).Materials and methodsThe optimal fluence of IMRT plans of ten patients of lung carcinoma, calculated using Eclipse TPS version 11.0 (Varian Medical Systems, Palo Alto, CA, USA), was used to generate the segmented MLC fields using our newly developed equally spaced (ES) reducing level and NSLS algorithms in MATLAB® version 2011b for 6–10 intensity levels. These MLC fields were imported into the plans with the same field setup and the final dose was recalculated. The results were compared with those of commercially available multiple static segments (MSS) leaf motion calculation (LMC) algorithm and few previously published algorithms. Plan scoring index (PSI) and degree of modulation (DoM) was calculated to compare the quality of different plans for the same patient.ResultsThe average differences in TotalMU and NS with respect to MSS algorithm are −3.80% and −14.28% for the NSLS algorithm, respectively. The calculated average PSI and DoM is 0.75, 2.51 and 0.91, 2.41 for the MSS and NSLS algorithms, respectively.ConclusionsIMRT plans generated using the NSLS algorithm resulted in the best PSI, DoM values among all the leaf sequencing algorithms. Our proposed NSLS algorithm allows bidirectional delivery in Varian medical linear accelerator which is not commercially available. NSLS algorithm is efficient in reducing the TotalMU and NS with equivalent plan quality as that of MSS

Dosimetric impact of contrast-enhanced 4d computed tomography for stereotactic body radiation therapy of hepatocelluar carcinoma

BACKGROUND: A purpose of the study was to investigate the dosimetric impact of contrast media on dose calculation using average 4D contrast-enhanced computed tomography (4D-CECT) and delayed 4D-CT (d4D-CT) images caused by CT simulation contrast agents for stereotactic body radiation therapy (SBRT) of liver cases. MATERIALS AND METHODS: Fifteen patients of liver SBRT treated using the volumetric modulated arc therapy (VMAT) technique were selected retrospectively. 4D-CECT, and d4D-CT were acquired with the Anzai gating system and GE CT. For all patients, gross target volume (GTV) was contoured on the ten phases after rigid registration of both the contrast and delayed scans and merged to generate internal target volume (ITV) on average CT images. Region of interest (ROI) was drawn on contrast images and then copied to the delayed images after rigid registration of two average CT datasets. The treatment plans were generated for contrast enhanced average CT, delayed average CT and contrast enhanced average CT with electron density of the heart overridden. RESULTS: No significant dosimetric difference was observed in plans parameters (mean HU value of the liver, total monitor units, total control points, degree of modulation and average segment area) except mean HU value of the aorta amongst the three arms. All the OARs were evaluated and resulted in statistically insignificant variation (p > 0.05) using one way ANOVA analysis. CONCLUSIONS: Contrast enhanced 4D-CT is advantageous in accurate delineation of tumors and assessing accurate ITV. The treatment plans generated on average 4D-CECT and average d4D-CT have a clinically insignificant effect on dosimetric parameters

Artificial Sequences and Complexity Measures

In this paper we exploit concepts of information theory to address the fundamental problem of identifying and defining the most suitable tools to extract, in a automatic and agnostic way, information from a generic string of characters. We introduce in particular a class of methods which use in a crucial way data compression techniques in order to define a measure of remoteness and distance between pairs of sequences of characters (e.g. texts) based on their relative information content. We also discuss in detail how specific features of data compression techniques could be used to introduce the notion of dictionary of a given sequence and of Artificial Text and we show how these new tools can be used for information extraction purposes. We point out the versatility and generality of our method that applies to any kind of corpora of character strings independently of the type of coding behind them. We consider as a case study linguistic motivated problems and we present results for automatic language recognition, authorship attribution and self consistent-classification.Comment: Revised version, with major changes, of previous "Data Compression approach to Information Extraction and Classification" by A. Baronchelli and V. Loreto. 15 pages; 5 figure

Development and validation of self-reported line drawings for assessment of knee malalignment and foot rotation: a cross-sectional comparative study

<p>Abstract</p> <p>Background</p> <p>For large scale epidemiological studies clinical assessments and radiographs can be impractical and expensive to apply to more than just a sample of the population examined. The study objectives were to develop and validate two novel instruments for self-reported knee malalignment and foot rotation suitable for use in questionnaire studies of knee pain and osteoarthritis.</p> <p>Methods</p> <p>Two sets of line drawings were developed using similar methodology. Each instrument consisted of an explanatory question followed by a set of drawings showing straight alignment, then two each at 7.5° angulation and 15° angulation in the varus/valgus (knee) and inward/outward (foot) directions. Forty one participants undertaking a community study completed the instruments on two occasions. Participants were assessed once by a blinded expert clinical observer with demonstrated excellent reproducibility. Validity was assessed by sensitivity, specificity and likelihood ratio (LR) using the observer as the reference standard. Reliability was assessed using weighted kappa (κ). Knee malalignment was measured on 400 knee radiographs. General linear model was used to assess for the presence of a linear increase in knee alignment angle (measured medially) from self-reported severe varus to mild varus, straight, mild valgus and severe valgus deformity.</p> <p>Results</p> <p>Observer reproducibility (κ) was 0.89 and 0.81 for the knee malalignment and foot rotation instruments respectively. Self-reported participant reproducibility was also good for the knee (κ 0.73) and foot (κ 0.87) instruments. Validity was excellent for the knee malalignment instrument, with a sensitivity of 0.74 (95%CI 0.54, 0.93) and specificity of 0.97 (95%CI 0.94, 1.00). Similarly the foot rotation instrument was also found to have high sensitivity (0.92, 95%CI 0.83, 1.01) and specificity (0.96, 95%CI 0.93, 1.00). The knee alignment angle increased progressively from self reported severe varus to mild varus, straight, mild valgus and severe valgus knee malalignment (p_trend<0.001).</p> <p>Conclusions</p> <p>The two novel instruments appear to provide a valid and reliable assessment of self-reported knee malalignment and foot rotation, and may have a practical use in epidemiological studies.</p

STAT3 inhibition with Galiellalactone effectively targets the prostate cancer stem-like cell population."

Cancer stem cells (CSCs) are a small subpopulation of quiescent cells with the potential to differentiate into tumor cells. CSCs are involved in tumor initiation and progression and contribute to treatment failure through their intrinsic resistance to chemo- or radiotherapy, thus representing a substantial concern for cancer treatment. Prostate CSCs’ activity has been shown to be regulated by the transcription factor Signal Transducer and Activator of Transcription 3 (STAT3). Here we investigated the effect of galiellalactone (GL), a direct STAT3 inhibitor, on CSCs derived from prostate cancer patients, on docetaxel-resistant spheres with stem cell characteristics, on CSCs obtained from the DU145 cell line in vitro and on DU145 tumors in vivo. We found that GL significantly reduced the viability of docetaxel-resistant and patient-derived spheres. Moreover, CSCs isolated from DU145 cells were sensitive to low concentrations of GL, and the treatment with GL suppressed their viability and their ability to form colonies and spheres. STAT3 inhibition down regulated transcriptional targets of STAT3 in these cells, indicating STAT3 activity in CSCs. Our results indicate that GL can target the prostate stem cell niche in patient-derived cells, in docetaxel-resistant spheres and in an in vitro model. We conclude that GL represents a promising therapeutic approach for prostate cancer patients, as it reduces the viability of prostate cancer-therapy-resistant cells in both CSCs and non-CSC populations

Hand osteoarthritis: clinical phenotypes, molecular mechanisms and disease management

Osteoarthritis (OA) is a highly prevalent condition and the hand is the most commonly affected site. Patients with hand OA frequently report symptoms of pain, functional limitations, and frustration in undertaking everyday activities. The condition presents clinically with changes to the bone, ligaments, cartilage and synovial tissue, which can be observed using radiography, ultrasonography or MRI. Hand OA is a heterogeneous disorder and is considered to be multifactorial in aetiology. This review provides an overview of the epidemiology, presentation and burden of hand OA, including an update on hand OA imaging (including the development of novel techniques), disease mechanisms and management. In particular, areas for which new evidence has substantially changed the way we understand, consider and treat hand OA are highlighted. For example, genetic studies, clinical trials and careful prospective imaging studies from the past 5 years are beginning to provide insights into the pathogenesis of hand OA that might uncover new therapeutic targets in disease